The major obstacle to long-term survival after lung transplantation is chronic graft dysfunction manifest as bronchiolitis obliterans. Since the early stages are characterized by proliferation of itinerant cells (lymphocytes and macrophages), we hypothesized that cytokines and chemokines may play a role in the development of the fibroproliferative process. In a heterotopic rat tracheal transplant model, we studied isografts and allografts 3, 7, and 21 d after transplantation as representative time points for the triphasic time course in the evolution of allograft airway obliteration. Using a semiquantitative RT-PCR technique, intragraft gene expression of T-helper 1 (Th1)- and Th2-type cytokines and of C-C and C-X-C chemokines was examined. The results of our study show a distinct pattern of cytokine and chemokine gene expression in the development of post-transplant airway obliteration. Allografts, in contrast to isografts, showed a strong and persistent Th1-type response (expression of interleukin-2 and interferon-gamma genes), even after fibrous airway obliteration was complete, suggesting an ongoing allo-immune process until late in the fibroproliferative stage. RANTES and MCP-1 were also upregulated late after transplantation, whereas MIP-2 upregulation occurred early post-transplant and was not restricted to allografts alone, which might reflect alloantigen-independent processes after transplantation that are present in both allografts and isografts.
Many models and real complex systems possess critical thresholds at which the systems shift dramatically from one sate to another. The discovery of early-warnings in the vicinity of critical points are of great importance to estimate how far the systems are away from the critical states. Multifractal Detrended Fluctuation analysis (MF-DFA) and visibility graph method have been employed to investigate the multifractal and geometrical properties of the magnetization time series of the two-dimensional Ising model. Multifractality of the time series near the critical point has been uncovered from the generalized Hurst exponents and singularity spectrum. Both long-term correlation and broad probability density function are identified to be the sources of multifractality. Heterogeneous nature of the networks constructed from magnetization time series have validated the fractal properties. Evolution of the topological quantities of the visibility graph, along with the variation of multifractality, serve as new early-warnings of phase transition. Those methods and results may provide new insights about the analysis of phase transition problems and can be used as early-warnings for a variety of complex systems.
LytA is responsible for the autolysis of many Streptococcus species, including pathogens such as S. pneumoniae, S. pseudopneumoniae and S. mitis. However, how this major autolysin achieves full activity remains unknown. Here, the full-length structure of the S. pneumoniae LytA dimer is reported at 2.1 Å resolution. Each subunit has an N-terminal amidase domain and a C-terminal choline-binding domain consisting of six choline-binding repeats, which form five canonical and one single-layered choline-binding sites. Site-directed mutageneses combined with enzymatic activity assays indicate that dimerization and binding to choline are two independent requirements for the autolytic activity of LytA in vivo. Altogether, it is suggested that dimerization and full occupancy of all choline-binding sites through binding to choline-containing TA chains enable LytA to adopt a fully active conformation which allows the amidase domain to cleave two lactyl-amide bonds located about 103 Å apart on the peptidoglycan.
Decreased nitric oxide (NO) production has been reported during lung transplantation in patients. To study the effects of ischemia and reperfusion on endogenous NO synthase (NOS) expression, both an ex vivo and an in vivo lung injury model for transplantation were used. Donor rat lungs were flushed with cold low-potassium dextran solution and subjected to either cold (4 degrees C for 12 h) or warm (21 degrees C for 4 h) ischemic preservation followed by reperfusion with an ex vivo model. A significant increase in inducible NOS and a decrease in endothelial NOS mRNA was found after reperfusion. These results were confirmed in a rat single-lung transplant model after warm preservation. Interestingly, protein contents of both inducible NOS and endothelial NOS increased in the transplanted lung after 2 h of reperfusion. However, the total activity of NOS in the transplanted lungs remained at very low levels. We conclude that ischemic lung preservation and reperfusion result in altered NOS gene and protein expression with inhibited NOS activity, which may contribute to the injury of lung transplants.
The properties of q-dependent cross-correlation matrices of stock market have been analyzed by using the random matrix theory and complex network. The correlation structures of the fluctuations at different magnitudes have unique properties. The cross-correlations among small fluctuations are much stronger than those among large fluctuations. The large and small fluctuations are dominated by different groups of stocks. We use complex network representation to study these q-dependent matrices and discover some new identities. By utilizing those q-dependent correlationbased networks, we are able to construct some portfolio by those most independent stocks which consistently perform the best. The optimal multifractal order for portfolio optimization is approximately q = 2. These results have deepened our understanding about the collective behaviors of the complex financial system.
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